Trauma is the leading cause of death between the ages of 1-44 years. Among late deaths, multiple organ system failure (MOSF) is a principal factor. The stage for MOSF may be set at the time of initial injury as a direct consequence of ischemia-reperfusion injury. The neutrophil (PNM) is an important mediator of ischemia-reperfusion injury, presumably as a result of increased adherence between PNMs and endothelial cells (EC). One major mechanisms of PMN-EC adherence is via the leucocyte adhesive protein complex CD11/CD18. We have developed a monoclonal antibody (MAb), designated MAb 60.3 to this complex. MAb 60.3 in vitro prevents PMN-PMN and PMN-EC adherence. In preliminary studies in a rabbit model of hemorrhagic shock, MAb 60.3 administered either pre-shock or at the time of resuscitation significantly increased survival and lessened acidosis and gross and histologic changes compared with control animals. In this application, we propose to continue these studies to address three areas: 1) We will extend these studies to a sub-human primate model of hemorrhagic shock, to verify that the preliminary observations are not species specific. 2) Because interference with PMN adherence may interfere with normal bacterial defense, we will investigate whether MAb 60.3 increases susceptibility to infection in a bactermia model and a peritonitis model. 3) In order to further elucidate the mechanisms of PMN - mediated ischemia-reperfusion injury we will use two models: a renal occlusion model and a rabbit ear free-flap model. These will permit clarification of the relative roles of PMN- EC adherence, proteases, and oxidants by examination of functional as well as histologic changes. These studies will provide essential information related to the role of PMNs in ischemia-reperfusion injury in hemorrhagic shock.